Impact of Treatment Response on Risk of Serious Infections in Patients With Crohn's Disease: Secondary Analysis of the PYRAMID Registry.

BACKGROUND & AIMS: Traditional risk factors for serious infections with advanced therapies in patients with Crohn's disease (CD) have been assessed at baseline before starting therapy. We evaluated the impact of treatment response on the risk of serious infections in adalimumab-treated patients with CD through secondary analysis of the PYRAMID registry (NCT00524537). METHODS: We included patients with CD who initiated adalimumab and classified them as treatment responders (achieved steroid-free clinical remission based on patient-reported outcomes) vs nonresponders (not in steroid-free clinical remission) at 6 months after treatment initiation (landmark). We compared the risk of serious infections between responders vs nonresponders between 6 and 36 months after treatment initiation through stabilized inverse probability of treatment weighting Cox proportional hazards model. RESULTS: Of 1515 adalimumab-treated patients, 763 (50.4%) were classified as responders at 6 months (37 ± 13 y; 56% female; disease duration, 9.5 ± 8.5 y). Compared with nonresponders, responders were less likely to have moderate to severe symptoms (55.6% vs 33%), or require steroids (45.5% vs 17.3%) or opiates (6.6% vs 1.3%) at baseline, without any differences in disease location, perianal disease, and prior CD complications. During follow-up evaluation, using stabilized inverse probability of treatment weighting, responders were 34% less likely to experience serious infections compared with nonresponders (hazard ratio, 0.66; 95% CI, 0.46-0.96). Risk of gastrointestinal and extraintestinal infections was lower in responders vs nonresponders. CONCLUSIONS: Patients with CD who respond to adalimumab have a lower risk of developing serious infections compared with nonresponders. These findings underscore that initiation of advanced therapy for CD may lower the risk of serious infections through effective disease control and avoidance of corticosteroids.

Efficient Massive MIMO Detection for M-QAM Symbols.

Massive multiple-input multiple-output (MIMO) systems significantly outperform small-scale MIMO systems in terms of data rate, making them an enabling technology for next-generation wireless systems. However, the increased number of antennas increases the computational difficulty of data detection, necessitating more efficient detection techniques. This paper presents a detector based on joint deregularized and box-constrained dichotomous coordinate descent (BOXDCD) with iterations for rectangular m-ary quadrature amplitude modulation (M-QAM) symbols. Deregularization maximized the energy of the solution. With the box-constraint, the deregularization forces the solution to be close to the rectangular boundary set. The numerical results demonstrate that the proposed detector achieves a considerable performance gain compared to existing detection algorithms. The performance advantage increases with the system size and signal-to-noise ratio.

Change in Albuminuria and GFR Slope as Joint Surrogate End Points for Kidney Failure: Implications for Phase 2 Clinical Trials in CKD.

SIGNIFICANCE STATEMENT: Changes in albuminuria and GFR slope are individually used as surrogate end points in clinical trials of CKD progression, and studies have demonstrated that each is associated with treatment effects on clinical end points. In this study, the authors sought to develop a conceptual framework that combines both surrogate end points to better predict treatment effects on clinical end points in Phase 2 trials. The results demonstrate that information from the combined treatment effects on albuminuria and GFR slope improves the prediction of treatment effects on the clinical end point for Phase 2 trials with sample sizes between 100 and 200 patients and duration of follow-up ranging from 1 to 2 years. These findings may help inform design of clinical trials for interventions aimed at slowing CKD progression. BACKGROUND: Changes in log urinary albumin-to-creatinine ratio (UACR) and GFR slope are individually used as surrogate end points in clinical trials of CKD progression. Whether combining these surrogate end points might strengthen inferences about clinical benefit is unknown. METHODS: Using Bayesian meta-regressions across 41 randomized trials of CKD progression, we characterized the combined relationship between the treatment effects on the clinical end point (sustained doubling of serum creatinine, GFR <15 ml/min per 1.73 m 2 , or kidney failure) and treatment effects on UACR change and chronic GFR slope after 3 months. We applied the results to the design of Phase 2 trials on the basis of UACR change and chronic GFR slope in combination. RESULTS: Treatment effects on the clinical end point were strongly associated with the combination of treatment effects on UACR change and chronic slope. The posterior median meta-regression coefficients for treatment effects were -0.41 (95% Bayesian Credible Interval, -0.64 to -0.17) per 1 ml/min per 1.73 m 2 per year for the treatment effect on GFR slope and -0.06 (95% Bayesian Credible Interval, -0.90 to 0.77) for the treatment effect on UACR change. The predicted probability of clinical benefit when considering both surrogates was determined primarily by estimated treatment effects on UACR when sample size was small (approximately 60 patients per treatment arm) and follow-up brief (approximately 1 year), with the importance of GFR slope increasing for larger sample sizes and longer follow-up. CONCLUSIONS: In Phase 2 trials of CKD with sample sizes of 100-200 patients per arm and follow-up between 1 and 2 years, combining information from treatment effects on UACR change and GFR slope improved the prediction of treatment effects on clinical end points.

Comparative Safety of Biologic Agents in Patients With Inflammatory Bowel Disease With Active or Recent Malignancy: A Multi-Center Cohort Study.

BACKGROUND & AIMS: Safety of biologic agents is a key consideration in patients with inflammatory bowel disease (IBD) and active or recent cancer. We compared the safety of tumor necrosis factor (TNF)-α antagonists vs non-TNF biologics in patients with IBD with active or recent cancer. METHODS: We conducted a multicenter retrospective cohort study of patients with IBD and either active cancer (cohort A) or recent prior cancer (within ≤5 years; cohort B) who were treated with TNFα antagonists or non-TNF biologics after their cancer diagnosis. Primary outcomes were progression-free survival (cohort A) or recurrence-free survival (cohort B). Safety was compared using inverse probability of treatment weighting with propensity scores. RESULTS: In cohort A, of 125 patients (483.8 person-years of follow-up evaluation) with active cancer (age, 54 ± 15 y, 75% solid-organ malignancy), 10 of 55 (incidence rate [IR] per 100 py, 4.4) and 9 of 40 (IR, 10.4) patients treated with TNFα antagonists and non-TNF biologics had cancer progression, respectively. There was no difference in the risk of progression-free survival between TNFα antagonists vs non-TNF biologics (hazard ratio, 0.76; 95% CI, 0.25-2.30). In cohort B, of 170 patients (513 person-years of follow-up evaluation) with recent prior cancer (age, 53 ± 15 y, 84% solid-organ malignancy; duration of remission, 19 ± 19 mo), 8 of 78 (IR, 3.4) and 5 of 66 (IR 3.7) patients treated with TNFα antagonists and non-TNF biologics had cancer recurrence, respectively. The risk of recurrence-free survival was similar between both groups (hazard ratio, 0.94; 95% CI, 0.24-3.77). CONCLUSIONS: In patients with IBD with active or recent cancer, TNFα antagonists and non-TNF biologics have comparable safety. The choice of biologic should be dictated by IBD disease severity in collaboration with an oncologist.

Conventional Frailty Index Does Not Predict Risk of Postoperative Complications in Patients With IBD: A Multicenter Cohort Study.

BACKGROUND: Frailty has been associated with adverse outcomes in patients with IBD. OBJECTIVE: This study aimed to evaluate the association between health deficit-defined frailty (using the 5-factor modified frailty index) and postoperative outcomes in patients with IBD. DESIGN: Prospective cohort study. SETTING: American College of Surgeons National Surgical Quality Improvement Program, Inflammatory Bowel Diseases Module. PATIENTS: The included patients had IBD and underwent major abdominal surgery between 2016 and 2019. Patients were classified as frail (modified frailty index ≥2), prefrail (modified frailty index = 1), or normal (modified frailty index = 0) based on a validated, 5-factor modified frailty index. MAIN OUTCOME MEASURES: The association was evaluated between frailty and risk of 30-day severe postoperative complications, prolonged hospital stay, and risk of readmission using multivariable logistic regression. RESULTS: Of 3172 patients with IBD who underwent major abdominal surgery (42.7 ± 16.4 y, 49.3% female, 57.7% with Crohn's disease, 43.9% on biologics), 116 (3.7%) were classified as frail and 477 as prefrail (15%). After adjustment for age, sex, race/ethnicity, smoking, BMI, type of surgery, corticosteroid use, and biologic and immunomodulator use, frailty was not associated with increased risk for severe postoperative complications (adjusted OR, 1.24; 95% CI, 0.81-1.90), mortality (adjusted OR, 1.38 [0.44-3.6]), or 30-day readmission (adjusted OR, 1.35 [0.77-2.30]). Nonelective surgery, significant weight loss, corticosteroid use, and need for ileostomy were associated with increased risk of severe postoperative complications. LIMITATIONS: Limited information regarding IBD-specific characteristics. CONCLUSIONS: In patients with IBD undergoing major abdominal surgery, frailty measured by a conventional abbreviated health deficits index is not predictive of adverse postoperative outcomes. Biologic and functional measures of frailty may better risk-stratify surgical candidacy in patients with IBDs. See Video Abstract at http://links.lww.com/DCR/C108 . EL NDICE DE FRAGILIDAD CONVENCIONAL NO PREDICE EL RIESGO DE COMPLICACIONES POSOPERATORIAS EN PACIENTES CON ENFERMEDADES INFLAMATORIAS DEL INTESTINO UN ESTUDIO DE COHORTE MULTICNTRICO: ANTECEDENTES:La fragilidad se ha asociado con resultados adversos en pacientes con enfermedades inflamatorias del intestino.OBJETIVO:Examinamos la asociación entre la fragilidad definida por déficit de salud (utilizando el índice de fragilidad modificado de 5 factores) y los resultados postoperatorios en pacientes con enfermedades inflamatorias del intestino.DISEÑO:Estudio de cohorte prospective.ESCENARIO:Programa Nacional de Mejoramiento de la Calidad Quirúrgica del Colegio Estadounidense de Cirujanos, Módulo de Enfermedades Inflamatorias del Intestino.PACIENTES:Pacientes con enfermedades inflamatorias intestinales inscritos en la cohorte que se sometieron a cirugía abdominal mayor entre 2016-19.EXPOSICIÓN:Los pacientes se clasificaron como frágiles (índice de fragilidad modificado ≥2), prefrágiles (índice de fragilidad modificado = 1) o normales (índice de fragilidad modificado = 0) según un índice de fragilidad modificado de 5 factores validado.PRINCIPALES MEDIDAS DE RESULTADO:Examinamos la asociación entre la fragilidad y el riesgo de complicaciones postoperatorias graves a los 30 días, la estancia hospitalaria prolongada y el riesgo de reingreso, mediante regresión logística multivariable.RESULTADOS:De 3172 pacientes con enfermedades inflamatorias intestinales que se sometieron a cirugía abdominal mayor (42,7 ± 16,4 años, 49,3% mujeres, 57,7% con enfermedad de Crohn, 43,9% con biológicos), 116 (3,7%) fueron clasificados como frágiles y 477 como pre- frágil (15%). Después de ajustar por edad, sexo, raza/origen étnico, tabaquismo, índice de masa corporal, tipo de cirugía, uso de corticosteroides, uso de biológicos e inmunomoduladores, la fragilidad no se asoció con un mayor riesgo de complicaciones postoperatorias graves (odds ratio ajustado, 1,24; 95 % de confianza intervalos, 0,81-1,90), mortalidad (odds ratio ajustado, 1,38 [0,44-3,6]) o reingreso a los 30 días (odds ratio ajustado, 1,35 [0,77-2,30]). La cirugía no electiva, la pérdida de peso significativa, el uso de corticosteroides y la necesidad de ileostomía se asociaron con un mayor riesgo de complicaciones posoperatorias graves.LIMITACIONES:Información limitada sobre las características específicas de la enfermedad inflamatoria intestinal.CONCLUSIONES:En pacientes con enfermedades inflamatorias del intestino sometidos a cirugía abdominal mayor, la fragilidad medida por un índice de déficit de salud abreviado convencional no es predictivo de resultados postoperatorios adversos. Las medidas biológicas y funcionales de fragilidad pueden estratificar mejor la candidatura quirúrgica en pacientes con enfermedades inflamatorias del intestino. Consulte el Video Resumen en http://links.lww.com/DCR/C108 . (Traducción-Yesenia Rojas-Khalil ).

Effectiveness and Safety of Biologic Therapy in Hispanic Vs Non-Hispanic Patients With Inflammatory Bowel Diseases: A CA-IBD Cohort Study.

BACKGROUND & AIMS: There are limited data on outcomes of biologic therapy in Hispanic patients with inflammatory bowel diseases (IBDs). We compared risk of hospitalization, surgery, and serious infections in Hispanic vs non-Hispanic patients with IBD in a multicenter, electronic health record-based cohort of biologic-treated patients. METHODS: We identified adult patients with IBD who were new users of biologic agents (tumor necrosis factor α [TNF-α] antagonists, ustekinumab, vedolizumab) from 5 academic institutions in California between 2010 and 2017. We compared the risk of all-cause hospitalization, IBD-related surgery, and serious infections in Hispanic vs non-Hispanic patients using 1:4 propensity score matching and survival analysis. RESULTS: We compared 240 Hispanic patients (53% male; 45% with ulcerative colitis; 73% TNF-α antagonist-treated; 20% with prior biologic exposure) with 960 non-Hispanic patients (51% male; 44% with ulcerative colitis; 67% TNF-α antagonist-treated; 27% with prior biologic exposure). After propensity score matching, Hispanic patients were younger (37 ± 15 vs 40 ± 16 y; P = .02) and had a higher burden of comorbidities (Elixhauser index, >0; 37% vs 26%; P < .01), without any differences in patterns of medication use, burden of inflammation, and hospitalizations. Within 1 year of biologic initiation, Hispanic patients had higher rates of hospitalizations (31% vs 23%; adjusted hazard ratio [aHR], 1.32; 95% CI, 1.01-1.74) and IBD-related surgery (7.1% vs 4.6%; aHR, 2.00; 95% CI, 1.07-3.72), with a trend toward higher risk of serious infections (8.8% vs 4.9%; aHR, 1.74; 95% CI, 0.99-3.05). CONCLUSIONS: In a multicenter, propensity score-matched cohort of biologic-treated patients with IBD, Hispanic patients experienced higher rates of hospitalization, surgery, and serious infections. Future studies are needed to investigate the biological, social, and environmental drivers of these differences.

Comparative Safety and Effectiveness of Biologic Therapy for Crohn's Disease: A CA-IBD Cohort Study.

BACKGROUND & AIMS: We compared the safety and effectiveness of tumor necrosis factor α (TNF-α) antagonists vs vedolizumab vs ustekinumab in patients with Crohn's disease (CD) in a multicenter cohort (CA-IBD). METHODS: We created an electronic health record-based cohort of adult patients with CD who were initiating a new biologic agent (TNF-α antagonists, ustekinumab, vedolizumab) from 5 health systems in California between 2010 and 2017. We compared the risk of serious infections (safety) and all-cause hospitalization and inflammatory bowel disease-related surgery (effectiveness) between different biologic classes using propensity score (PS) matching. RESULTS: As compared with TNF-α antagonists (n = 1030), 2:1 PS-matched, ustekinumab-treated patients with CD (n = 515) experienced a lower risk of serious infections (hazard ratio [HR], 0.36; 95% CI, 0.20-0.64), without any difference in the risk of hospitalization (HR, 0.99; 95% CI, 0.89-1.21) or surgery (HR, 1.08; 95% CI, 0.69-1.70). Compared with vedolizumab (n = 221), 1:1 PS-matched, ustekinumab-treated patients with CD (n = 221) experienced a lower risk of serious infections (HR, 0.20; 95% CI, 0.07-0.60), without significant differences in risk of hospitalization (HR, 0.76; 95% CI, 0.54-1.07) or surgery (HR, 1.42; 95% CI, 0.54-3.72). Compared with TNF-α antagonists (n = 442), 2:1 PS-matched, vedolizumab-treated patients with CD (n = 221) had a similar risk of serious infections (HR, 1.53; 95% CI, 0.84-2.78), hospitalization (HR, 1.32; 95% CI, 0.98-1.77), and surgery (HR, 0.63; 95% CI, 0.27-1.47). High comorbidity burden, concomitant opiate use, and prior hospitalization were associated with serious infections and hospitalization in biologic-treated patients with CD. CONCLUSION: In a multicenter cohort of biologic-treated patients with CD, ustekinumab was associated with a lower risk of serious infections compared with TNF-α antagonists and vedolizumab, without any differences in risk of hospitalization or surgery. The risk of serious infections was similar for TNF-α antagonists vs vedolizumab.

Impact of recurrent hospitalization for Clostridioides difficile on longitudinal outcomes in patients with inflammatory bowel diseases: a nationally representative cohort.

Background: Clostridioides difficile infection (CDI) is associated with poor outcomes in patients with inflammatory bowel diseases (IBD). Objectives: We conducted a nationally representative cohort study to evaluate the impact of recurrent CDI (rCDI)-related hospitalization on longitudinal unplanned healthcare utilization in patients with IBD. Design: This was a retrospective cohort study that utilized the 2017 Nationwide Readmissions Database (NRD). Methods: We identified 13,446 patients with IBD, hospitalized at least twice from January to June 2017 and followed through December 2017; of these, 1,148 had CDI-related hospitalizations. We compared the annual burden of hospitalization and IBD-related surgery in IBD patients with rCDI-related admission versus single CDI-related admission (primary reference), and those with one or more CDI-related admission versus no CDI-related admission (secondary reference). Results: There were no significant differences in risk and burden of unplanned healthcare utilization (time spent in-hospital, 27 days versus 27 days, p = 0.62), 6-month readmission (63% versus 64.3%, p = 0.8) or IBD-related surgery in patients with recurrent (two or more) CDI-related hospitalizations versus single CDI-related admission. However, patients with ⩾1 CDI-related admission versus no CDI admissions experienced higher rate of 6-month readmission (61.1% versus 55.7%, p<.001), total days spent in the hospital per year (median: 26 days versus 21 days, p<.001), total cost across all hospitalizations per year ($212,524 versus $184,384, p < 0.01), and inpatient mortality (3.28% versus 1.81%, p = 0.01), without an increase in risk of IBD-related surgery (6.7% versus 6.4%, p = 0.79). Conclusion: While patients with IBD hospitalized for CDI have poor longitudinal inpatient outcomes, recurrent admissions for CDI may not increase risk of adverse outcomes compared to one-time admission.

Effect of Obesity on Risk of Hospitalization, Surgery, and Serious Infection in Biologic-Treated Patients With Inflammatory Bowel Diseases: A CA-IBD Cohort Study.

INTRODUCTION: Obesity is variably associated with treatment response in biologic-treated patients with inflammatory bowel diseases (IBD). We evaluated the association between obesity and risk of hospitalization, surgery, or serious infections in patients with IBD in new users of biologic agents in a large, multicenter, electronic health record (EHR)-based cohort (CA-IBD). METHODS: We created an EHR-based cohort of adult patients with IBD who were new users of biologic agents (tumor necrosis factor [TNF-α] antagonists, ustekinumab, and vedolizumab) between January 1, 2010, and June 30, 2017, from 5 health systems in California. Patients were classified as those with normal body mass index (BMI), overweight, or obese based on the World Health Organization classification. We compared the risk of all-cause hospitalization, IBD-related surgery, or serious infections among patients with obesity vs those overweight vs those with normal BMI, using Cox proportional hazard analyses, adjusting for baseline demographic, disease, and treatment characteristics. RESULTS: Of 3,038 biologic-treated patients with IBD (69% with Crohn's disease and 76% on TNF-α antagonists), 28.2% (n = 858) were overweight, and 13.7% (n = 416) were obese. On a follow-up after biologic initiation, obesity was not associated with an increased risk of hospitalization (adjusted hazard ratio [aHR] vs normal BMI, 0.90; [95% confidence interval, 0.72-1.13]); IBD-related surgery (aHR, 0.62 [0.31-1.22]); or serious infection (aHR, 1.11 [0.73-1.71]). Similar results were observed on stratified analysis by disease phenotype (Crohn's disease vs ulcerative colitis) and index biologic therapy (TNF-α antagonists vs non-TNF-α antagonists). DISCUSSION: In a multicenter, EHR-based cohort of biologic-treated patients with IBD, obesity was not associated with hospitalization, surgery, or serious infections. Further studies examining the effect of visceral obesity on patient-reported and endoscopic outcomes are needed.

Trends in U.S. Health Care Spending on Inflammatory Bowel Diseases, 1996-2016.

BACKGROUND: Inflammatory bowel diseases (IBD) are rising in prevalence and are associated with high health care costs. We estimated trends in U.S. health care spending in patients with IBD between 1996 and 2016. METHODS: We used data on national health care spending developed by the Institute for Health Metrics and Evaluations for the Disease Expenditure Project. We estimated corresponding U.S. age-specific prevalence of IBD from the Global Burden of Diseases Study. From these 2 sources, we estimated prevalence-adjusted, temporal trends in U.S. health care spending in patients with IBD, stratified by age groups (<20 years, 20-44 years, 45-64 years, ≥65 years) and by type of care (ambulatory, inpatient, emergency department [ED], pharmaceutical prescriptions, and nursing care), using joinpoint regression, expressed as an annual percentage change (APC) with 95% confidence intervals. RESULTS: Overall, annual U.S. health care spending on IBD increased from $6.4 billion (95% confidence interval, 5.7-7.4) in 1996 to $25.4 billion (95% confidence interval, 22.4-28.7) in 2016, corresponding to a per patient increase in annual spending from $5714 to $14,033. Substantial increases in per patient spending on IBD were observed in patients aged ≥45 years. Between 2011 and 2016, inpatient and ED care accounted for 55.8% of total spending and pharmaceuticals accounted for 19.9%, with variation across age groups (inpatient/ED vs pharmaceuticals: ages ≥65 years, 57.6% vs 11.2%; ages 45-64 years, 49.5% vs 26.9%; ages 20-44 years, 59.2% vs 23.6%). CONCLUSIONS: Even after adjusting for rising prevalence, U.S. health care spending on IBD continues to progressively increase, primarily in middle-aged and older adults, with unplanned health care utilization accounting for the majority of costs.

Paternal Exposure to Immunosuppressive and/or Biologic Agents and Birth Outcomes in Patients With Immune-Mediated Inflammatory Diseases.

BACKGROUND & AIMS: We conducted a retrospective cohort study to inform the safety of exposure to immunosuppressive and/or biologic agents around conception in expectant fathers with immune-mediated inflammatory diseases (IMIDs) on birth outcomes. METHODS: Using a deidentified administrative claims database (OptumLabs Data Warehouse), we identified 7453 expectant fathers with IMIDs (inflammatory bowel diseases, rheumatoid arthritis, psoriasis/psoriatic arthritis, and ankylosing spondylitis) linked to newborns with periconception medication exposure between 38 and 60 weeks before the newborn birth date (34-58 weeks prior for preterm newborns) and neonatal follow-up for 3 months after the birth date. Through logistic regression adjusting for paternal age and race (and, in a subset, for maternal age, race, presence of IMIDs, and nonsingleton births), we compared the risk of major congenital malformations (primary outcome) and preterm birth and low birth weight in fathers exposed to thiopurines (n = 461), methotrexate (n = 171), tumor necrosis factor (TNF) α antagonists (n = 1082), or non-TNF-targeting biologic agents (n = 132) vs fathers not exposed to any of these medications (n = 5607). RESULTS: As compared to unexposed fathers (3.4% prevalence of major congenital malformations), exposure to thiopurines (relative risk [RR], 1.12; 95% confidence interval [CI], 0.66-1.76), methotrexate (RR, 0.67; 95% CI, 0.21-1.55), TNF-α antagonists (RR, 1.14; 95% CI, 0.81-1.57), and non-TNF-targeting biologic agents (RR, 1.75; 95% CI, 0.80-3.24) was not associated with increased risk of major congenital malformations. No association was observed between paternal medication exposure and risk of preterm birth or low birth weight. Results were stable on subanalyses of linked father-mother-newborn triads. CONCLUSIONS: In a large cohort study of 7453 expectant fathers with IMIDs, exposure to immunosuppressive or biologic agents around conception was not associated with increased risk of adverse birth outcomes.

Burden and Outcomes of Fragmentation of Care in Hospitalized Patients With Inflammatory Bowel Diseases: A Nationally Representative Cohort.

BACKGROUND: Fragmentation of care (FoC) may adversely impact health care quality in patients with chronic diseases. We conducted a US nationally representative cohort study to evaluate the burden and outcomes of FoC in hospitalized patients with inflammatory bowel disease (IBD). METHODS: Using Nationwide Readmissions Database 2013, we created 2 cohorts of superutilizer patients with IBD with 2 hospitalizations (cohort 1: FoC, defined as readmission to nonindex hospital vs no FoC) or 3 hospitalizations (cohort 2: multiple episodes of fragmentation vs single episode of fragmentation vs no FoC) between January and June 2013, which were followed through December 2013. We evaluated burden, pattern, and outcomes of fragmentation (6-month risk of readmission, risk of surgery, and inpatient mortality). RESULTS: In cohort 1, of 6073 patients with IBD with 2 admissions within 6 months, 1394 (23%) experienced FoC. Fragmentation of care was associated with modestly higher risk of readmission within 6 months (31% vs 28%, P < 0.01; adjusted relative risk, 1.11 [1.01-1.21]), without differences in risk of surgery (2.8% vs 4.3%, P = 0.19) or in-hospital mortality (0.2% vs 0.5%, P = 0.22). In cohort 2, of 1717 patients with 3 hospitalizations within 6 months, the number of patients with multiple episodes of fragmentation was associated with higher risk of readmission compared with patients with single episode of fragmentation or no FoC (52% vs 49% vs 43%, P = 0.03). CONCLUSIONS: In a US cohort study, FoC is associated with a modestly higher risk of readmission, without higher risk of surgery or mortality in superutilizer patients with IBD. Future studies focusing on impact of outpatient care and postdischarge coordination are warranted in superutilizer patients.

Disease- and Treatment-related Complications in Older Patients With Inflammatory Bowel Diseases: Comparison of Adult-onset vs Elderly-onset Disease.

BACKGROUND: The incidence and prevalence of inflammatory bowel diseases (IBD) in older adults are rising. There is a limited comparative assessment of risk of disease- and treatment-related complications in older patients (older than 60 years) with adult-onset (age at disease onset, 18-59 years; AO-IBD) vs elderly-onset IBD (age at disease onset, older than 60 years; EO-IBD). We compared clinical outcomes in older patients with IBD with AO-IBD vs EO-IBD. METHODS: We conducted a retrospective cohort study comparing risk of disease-related complications (IBD-related surgery, hospitalization, treatment escalation, clinical flare, or disease complication) and treatment-related complications (serious infection, malignancy, or death) in older patients with AO-IBD vs EO-IBD through Cox proportional hazard analysis, adjusting for age at cohort entry, disease phenotype, disease duration, prior surgery and/or hospitalization, medication use, disease activity at cohort entry, and comorbidities. RESULTS: We included 356 older patients with IBD (AO-IBD, 191 patients, 67 ± 5 y at cohort entry; EO-IBD, 165 patients, 72 ± 8 y at cohort entry). No significant differences were observed in the risk of disease-related complications in older patients with prevalent vs incident IBD (adjusted hazard ratio [aHR], 0.85; 95% CI, 0.58-1.25), although risk of IBD-related surgery was lower in older patients with prevalent IBD (aHR, 0.47; 95% CI, 0.25-0.89). Older patients with prevalent IBD were significantly less likely to experience treatment-related complications (aHR, 0.58; 95% CI, 0.39-0.87). CONCLUSION: Patients with AO-IBD have lower risk of treatment-related complications as they age compared with patients with EO-IBD, without a significant difference in risk of disease-related complications.